rs3751663

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_021098.3(CACNA1H):c.2031G>A(p.Ser677Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000312 in 1,572,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.73

Publications

2 publications found

Variant links:

Genes affected

CACNA1H (HGNC:1395): (calcium voltage-gated channel subunit alpha1 H) This gene encodes a T-type member of the alpha-1 subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. The alpha-1 subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants, encoding different isoforms, have been characterized for the gene described here. Studies suggest certain mutations in this gene lead to childhood absence epilepsy (CAE). [provided by RefSeq, Jul 2008]

CACNA1H Gene-Disease associations (from GenCC):

hyperaldosteronism, familial, type IV
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
childhood absence epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
epilepsy, childhood absence, susceptibility to, 6
Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

CACNA1H links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-1204038-G-A is Benign according to our data. Variant chr16-1204038-G-A is described in ClinVar as [Benign]. Clinvar id is 529596.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.73 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000324 (46/1420222) while in subpopulation EAS AF = 0.000777 (29/37336). AF 95% confidence interval is 0.000555. There are 0 homozygotes in GnomAdExome4. There are 23 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAdExome4 at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 35	ENST00000348261.11	NP_066921.2	O95180-1B3KQH9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1H	ENST00000348261.11 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 34	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 34	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 35	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.1992G>A	p.Ser664Ser	synonymous_variant	Exon 10 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 34	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.1992G>A	p.Ser664Ser	synonymous_variant	Exon 10 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.2031G>A	p.Ser677Ser	synonymous_variant	Exon 10 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.2031G>A		non_coding_transcript_exon_variant	Exon 10 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.2031G>A		non_coding_transcript_exon_variant	Exon 10 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.2031G>A		non_coding_transcript_exon_variant	Exon 10 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.1414G>A		non_coding_transcript_exon_variant	Exon 10 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*1478G>A		non_coding_transcript_exon_variant	Exon 9 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.2031G>A		non_coding_transcript_exon_variant	Exon 10 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.2031G>A		non_coding_transcript_exon_variant	Exon 10 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.2031G>A		non_coding_transcript_exon_variant	Exon 10 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.2031G>A		non_coding_transcript_exon_variant	Exon 10 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.2031G>A		non_coding_transcript_exon_variant	Exon 10 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.2031G>A		non_coding_transcript_exon_variant	Exon 10 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.2031G>A		non_coding_transcript_exon_variant	Exon 10 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.2031G>A		non_coding_transcript_exon_variant	Exon 10 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.2031G>A		non_coding_transcript_exon_variant	Exon 10 of 35			ENSP00000518777.1
CACNA1H	ENST00000711442.1 link	n.*1478G>A		3_prime_UTR_variant	Exon 9 of 34			ENSP00000518758.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

183994

AF XY:

0.0000199

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000738

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000129

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000324

AC:

AN:

1420222

Hom.:

Cov.:

AF XY:

0.0000327

AC XY:

AN XY:

702834

show subpopulations

African (AFR)

AF:

0.0000308

AC:

AN:

32472

American (AMR)

AF:

0.00

AC:

AN:

39838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25408

East Asian (EAS)

AF:

0.000777

AC:

AN:

37336

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.0000128

AC:

AN:

1091878

Other (OTH)

AF:

0.0000170

AC:

AN:

58838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.000131

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV

Benign:1

Jul 30, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.20

(source)

DANN

Benign

0.73

PhyloP100

-4.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs3751663

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over